Influence of age on innate and adaptive immunity in COVID-19 patients

By Nidhi Saha, BDSOct 21 2021Reviewed by Benedette Cuffari, M.Sc.

The current coronavirus disease 2019 (COVID-19) pandemic has posed a major public health crisis and has affected all nations across the globe. The disease is caused by the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is associated with rapid human transmission.

Study: Effect of Age on Innate and Adaptive Immunity in Hospitalized COVID-19 Patients. Image Credit: Soonthorn Wongsaita / Shutterstock.com

Background

COVID-19 can manifest with symptoms ranging from mild cough and cold to severe pneumonia, while some individuals may also be asymptomatic carriers. Patients usually present with common flu-like symptoms 3-7 days after exposure to the virus.

Recent evidence supports the strong association of innate immunity in determining COVID-19 severity. Notably, aging is a predisposing factor to severe disease and poor prognosis, as it is associated with a physiological decline in immune competence and dysregulated inflammatory response.

A new study published in the Journal of Clinical Medicine investigates how age influences SARS-CoV-2 replication, innate and adaptive immune responses, as well as clinical outcomes among recently hospitalized COVID-19 patients.

About the study

The present study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of Aarhus University Hospital.

Overall, 205 polymerase chain reaction (PCR)-confirmed hospitalized COVID-19 patients were included in the current study. Peripheral blood mononuclear cells (PBMCs), plasma, nasopharyngeal swabs, and clinical data, such as days of symptom onset, were collected from all patients. Participants were divided into two groups, of which included those below 65 years (116 patients) and those above 65 years (89 patients).

Study findings

It was noted that patients younger than 65 years had a higher median time to symptom onset post-hospital admission as compared to the higher age group. However, younger patients elicited more symptoms like coughing, dyspnea, fatigue, and headache. Comparatively, patients in the higher age group had more comorbidities and greater chances of requiring nasal oxygen therapy upon admission.

Quantification from oropharyngeal swabs found that COVID-19 patients over the age of 65 had a significantly higher viral load in the first eight days of symptom onset. Viral genome sequencing revealed that the predominant SARS-CoV-2 strain of B.1.177 was present in 50% and 27.4% in the younger than 65 years group and older than 65 years, respectively. In addition, the higher age group patients had increased C-reactive protein (CRP), increased ferritin, and increased interleukin 6 (IL-6) levels, along with longer time-to-recovery and higher disease progression to intensive care unit admission or death.

Comparatively, patients younger than 65 years exhibited significantly higher expression of classical monocytes including CD169 and CD47 in the first eight days of symptom onset, along with increased expression of intermediate monocytes. Consistent with these findings, higher levels of natural killer (NK) cell activation, cytokine-producing capacity, and secreted IL-2 were recorded among the younger than 65 years group.

Overall, aging was found to be a major risk factor for hyper-inflammation, poor virological control, and COVID-19 disease progression among the older group of patients.

Dendritic cells (DCs), which harbor immune regulatory functions crucial for COVID-19 outcomes, exhibit poorer activation and diminished antigen cross-presentation capacity among geriatric patients. The results also showed reduced NK cell maturation, as well as differentiation and functional markers, in patients above the age of 65 years.

Furthermore, reduced activation of effector and memory CD8 T-cells, as well as reduced plasma interferon γ (IFN-γ) levels, were reported among the older than 65 years group. The increased CD8 T-cell exhaustion (PD-1 expression) in the older than 65 years group correlated with the immune invasion strategy of SARS-CoV-2, thereby indicating the disruption of early T-cell response in this population.

Conclusion

The findings presented here suggest strong associations between aging, SARS-CoV-2 viral load, inflammation, and the prognosis of the disease. Geriatric patients have reduced monocyte activation, reduced monocyte antigen presentation capacity, and increased IFN γ-induced protein 10 (IP-10) cytokine levels in the early phase of symptomatic COVID-19, which may contribute to severe disease.

These findings confirm that aging interferes with the balance between cellular innate immune and proinflammatory responses during SARS-CoV-2 infection. Collectively, the findings depict impaired innate and adaptive immunity among the elderly during the early phase of the infection, which likely transpires into a lack of virological control and higher risk of disease progression in COVID-19.